This Application is submitted in response to PA-09-238 "Exfoliated Cells and Circulating DNA in Cancer Detection and Diagnosis" under the R21 funding mechanism. The work proposed in this application is aimed at developing automatic screening methods for oral and nasopharyngeal cancer, based on Spectral Cytopathology (SCP) which is a new diagnostic method based on a spectroscopic measurement of individual cells coupled to computer-based analysis. Proof-of-principle for detecting abnormal cells from the oral cavity via SCP was achieved, and identification of abnormal cells was found to be possible even before morphological changes occur in the cells. This proposal emphasizes the clinical significance of oral cancer screening by spectral methods;furthermore, it will extend the study to other parts of the head-and-neck (H&N) region, and collect datasets of sufficient size to attract other funding mechanisms to take this research to a commercial product. Oral and H&N cancer screening was selected for a target because such screening is not being carried out at this point, although cancers of the oral cavity are a major health problem, with a mean 5- year survival rate less than that of cancers which are more in the public's view, such Hodgkin's lymphoma, testicular cancer, or malignant melanoma. As in all epithelial cancers, early detection and treatment will increase the survival rate from H&N cancers, which presently are detected often after they have penetrated deeply into the surrounding tissue, or have formed metastases. SCP-based oral and H&N cancer screening can be carried out as easily as cervical cancer screening, and will reduce the complications and mortality from this disease.